Abnormal immune mechanisms are being studied in patients with primary biliary cirrhosis (PBC). T cell mediated help and suppression of pokeweed mitogen-induced immunoglobulin synthesis by B cells has been studied using radioimmunoassays to measure IgG and IgM synthesized by cultures containing appropriate mixtures of different lymphocyte subpopulations in vitro. The ability of T cells to proliferate when cultured with either autologous or allogeneic irradiated B cells (mixed lymphocyte reactions) or with hapten-modified autologous irradiated B cells has been assessed. Results of these studies include the demonstration in PBC of (i) a diminished capacity of T cells to inhibit immunoglobulin synthesis in vitro; (ii) a deficiency of the autologous but not the allogeneic mixed lymphocyte reaction and (iii) a deficiency in the primary but not the secondary proliferative response of T cells to hapten-modified cells. These findings suggest that in PBC there is a fundamental defect in the interaction between autoreactive T cells and surface antigens on autologous non-T cells which leads to diminished activation of suppressor T cells and hence predisposes to a state of immune hyperresponsiveness.